Abstract
Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3014-3025 |
| Number of pages | 12 |
| Journal | Clinical Cancer Research |
| Volume | 24 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 1 2018 |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. / Kalli, Kimberly R.; Block, Matthew S; Kasi, Pashtoon M.; Erskine, Courtney L.; Hobday, Timothy James; Dietz, Allan B; Padley, Douglas; Gustafson, Michael; Shreeder, Barath; Puglisi-Knutson, Danell; Visscher, Daniel W; Mangskau, Toni K.; Wilson, Glynn; Knutson, Keith L.
In: Clinical Cancer Research, Vol. 24, No. 13, 01.07.2018, p. 3014-3025.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients
AU - Kalli, Kimberly R.
AU - Block, Matthew S
AU - Kasi, Pashtoon M.
AU - Erskine, Courtney L.
AU - Hobday, Timothy James
AU - Dietz, Allan B
AU - Padley, Douglas
AU - Gustafson, Michael
AU - Shreeder, Barath
AU - Puglisi-Knutson, Danell
AU - Visscher, Daniel W
AU - Mangskau, Toni K.
AU - Wilson, Glynn
AU - Knutson, Keith L
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.
AB - Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.
UR - http://www.scopus.com/inward/record.url?scp=85049365468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049365468&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-17-2499
DO - 10.1158/1078-0432.CCR-17-2499
M3 - Article
VL - 24
SP - 3014
EP - 3025
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -